Device for determining the dissolution time of medicaments in pressed form, like tablets, pills or capsules

ABSTRACT

The invention relates to a device for determining the dissolution time of medication in pressed form, like tablets and capsules, (especially to DAB 10, 3rd Supplement 1994, or the European Pharmacopoeia or USP [USA]), consisting of a frame (1) with a central column (7) and a base plate (3, 10) having a plurality of holes (5, 5&#39;, 11) covered from below by a mesh (4). Test tubes (6, 6&#39;) are arranged upright in said holes inside the frame (1). A disk (8, 15) can be movably inserted into said test tubes to weight the individual pressed medication. An electric coil (12) is disposed around each hole (11) and on and/or in the base plate (10), wherein the electric coil forms part of an electrical oscillation circuit (17). A conductor loop (16) is disposed on and/or in the disk (15) for damping the electrical oscillation circuit (17) depending on distance. The electric coil (12) and the conductor loop (16) together are connected to an electric supply and evaluation device (20, 23) to generate oscillations and evaluate the measurement results.

TECHNICAL FIELD

The invention relates to a device for determining the dissolution timeof medicaments in pressed form, such as tablets, pills, or capsules,wherein the device comprises a frame with a center column and a baseplate, wherein the base plate comprises a plurality of holes, whereinthe holes are covered from below by a mesh, and wherein test tubes arearranged upright in the holes within the frame, wherein a disk ismovably inserted into each test tube for weighting the individualmedication, according to the preamble of claim 1.

STATE OF THE ART

The measurement of the dissolution time of medication in pressed form,such as tablets and capsules, is performed in a standardized testingset-up in order to assure the reproduceability of the measurementresults (in particular to DAB 10, 3rd Supplement 1994 or EuropeanPharmacopoeia or USP [USA]). It is determined based on the dissolutiontesting whether the tablets or capsules dissolve in a liquid mediumwithin the prescribed time under precisely set-forth conditions. Themain part of the apparatus comprises a rigid frame which contains sixcylindrical test tubes made of glass. Each tube is provided with acylindrical disk made of a transparent plastic material of a preciselyspecified relative density and size. The test tubes are supported intheir upright position by an upper and a lower transparent plate made ofplastic, wherein the plate comprises in each case six boreholes. Allboreholes have the same distance from the center point and the samedistance from one another. A mesh made of a stainless steel wire isdisposed at the underside of the lower plate. A metal column is disposedsuch at the center of the plate that the apparatus can be suspended fromthe metal column in a suspension arrangement and can be uniformly movedupward and downward by 50 to 60 mm with a motor 28 to 32 times perminute. For this purpose, the apparatus is suspended in a suitablecontainer comprising the prescribed liquid. After filling one tablet orcapsule into each tube and weighting the tube with the disk, thedetermination of the dissolution time of the tablets or capsules isperformed by observation of the measurement device and time-keeping bythe operating person.

A dissolution device for test bodies, in particular tablets, is knownfrom the German printed patent document DE 35 20 034 C1, wherein thetest bodies are disposed in containers of a dissolution basket between aHall generator and a disk provided with a magnet. The containers of thedissolution basket are heated with a heating installation to a constanttemperature. Once the test body dissolves, the disk moves together withthe magnet toward the Hall generator such that the Hall generator emitsa signal, wherein the signal can be fed to and displayed on a recordingdevice upon exceeding of a sound threshold. The transmission of theenergy for the electrical circuits in the dissolution basket occursthrough contacts or with a high-frequency transmitter arid ahigh-frequency receiver. The transmission of the signals to therecording device is performed with optoelectronic components.

An automatic dissolution-time measurement device for the pharmaceuticalquality control and production control of tablets and dragees or coatedtablets in a conductive test liquid is known from the German printedpatent document DE 94 19 245 U1, wherein the measurement devicecomprises a basket-like frame disposed in a beaker with a plurality ofglass tubes disposed in the frame. The bases of the glass tubes areformed by circular sieve or mesh bottom plates as supporting bottomfaces for the glass tubes. Each mesh bottom plate is comprised of twocurrent-carrying, electrode-forming wire-mesh halves, wherein thewire-mesh halves are disposed at a spacing from one another therebyforming a slot in between. A test sample is disposed in each glass tube.The test sample is covered with a floating body or floater which restson the test sample. The floater exhibits at its underside an embeddedcontact framework made of a metallic material. The conductivity of thetest liquid changes upon motion of the beaker and dissolution of thetablets, wherein the conductivity can be measured between the wire-meshhalves and the contact framework.

A tablet-disintegration time measurement device with agitated tubes in abath liquid is known from the U.S. printed patent document 3,618,395.This measurement device includes a plurality of opposed, spacedelectrodes at the base of the tablet-containing tubes. The presence of atablet disturbs an electromagnetic field set up at the electrodes,wherein the disturbance actuates a timer, and wherein the signals of thetimer can be evaluated.

Previous attempts for a fully automatic measurement always resulted ininadmissible changes of the test apparatus. Such changes are howeveronly admissible to a very small degree according to DAB 10.

Technical Object

It is an object of the invention to provide for a device of theinitially recited kind, which device captures in a contactless way themotion of the disks within the device without changing the prescribedparameters for the apparatus according to DAB 10, and which device is todetermine continuously the decreasing thickness or the residualthickness of the medication in pressed form such as tablets, pills, orcapsules during the dissolution process. In addition, the disks and theframes are to be interchangeable without having to carry out a newcalibration of the device; as in the past, the disks and frames are tobe easy to clean, without thereby influencing the measurement system.

Disclosure of the Invention and its Advantages

The solution of the object lies according to the invention in that anelectric coil is disposed around each hole on and/or in the base plateof the frame, wherein the electric coil forms part of an electricaloscillation circuit. A conductor loop is disposed on and/or in the diskfor path-dependently damping the electrical oscillation circuit. Theelectric coil and the conductor loop are jointly connected to anelectric supply device and an electric evaluation device to generateoscillations and to evaluate the measurement results.

Normally, the residual thickness is preset as set value. When the actualvalue of the medication is less than the residual thickness, then it isdeemed that the medication is dissolved.

The device is structured in an advantageous way such that the geometryand the density of the disks as well as the geometry of the test tubesand the structure of the mesh base of the frame remain unchanged. Inaddition, the disks and the frames are interchangeable without requiringa new calibration of the device.

In an advantageous way, the coil can be formed as single-layer coil oras multi-layer coil on a separate coil support, wherein the coil supportis either resting on the base plate of the frame, or is integrated intothe base plate of the frame, or is identical with the base plate of theframe. Each coil can be a flat coil, wherein one half of the windings ofthe flat coil are integrated into the upper side and the other half intothe underside of the base plate or, respectively, the coil support. Thelines to the coils are formed congruent relative to the upper side andunderside of the base plate or, respectively, of the coil support. Inaddition, the coils can be disposed in multi-layer technique on amulti-layer plate serving as a base plate or, respectively, as a coilsupport, and the coils can also be disposed within a coil base or,respectively, coil support separated from the base plate of the frame.

A mutual influencing of the measuring points or, respectively, of theoscillation circuits is avoided in that the electrical oscillationcircuits are controllable with a multiplexer, wherein the multiplexer ineach case energizes only one oscillation circuit.

The energy supply and the data transfer is performed preferablycontactless by means of a magnetic field between the frame and a driveunit, wherein the frame is supported within the drive unit with thecenter column.

In addition, the electric coupling path can in each case be comprised ofone half of a pot core or shell-type core with inserted coil on eachside, wherein on the driving side the shell-type core half with coil isintegrated into the support for the frame or, respectively, for thecenter column, and on the side of the frame the shell-type core halfwith coil is integrated into the center column.

The sensors comprised of oscillation circuits, evaluation device as wellas inductive energy coupling and data coupling can preferably beswitched to a common bus and receive a bus address, wherein a transportaddress is inserted into the message to be delivered for the paralleloperation of the sensors at the bus. The transmitter and receiver coilsof the sensors for coupling to the driving unit can be operated withdiffering frequencies for the separation of the energy and data flow.

A change of the density of the disks by the insertion of the conductorloop is compensated for by a hollow space in the interior of the disk,if it should be necessary.

The oscillation circuit coils are advantageously formed by conductorpaths within the base plate, wherein the conductor paths surround therespective test tubes. The spatial expansion of the field is limitedbased on the small length of the coils such that an influencing of theoscillation circuit by the mesh bottom plates of the frame is small. Amutual influencing of the measuring points is prevented with the use ofthe multiplexer.

Short description of the drawing, in which is shown:

FIGS. 1 a, b, c a device of the state of the art according to DAB 10;

FIG. 2 a base plate including holes for the insertion of the test tubes,wherein coils are formed around the holes on the base plate for theformation of oscillation circuits;

FIG. 3 a disk, as it is inserted into each test tube;

FIG. 4 a block diagram of the electric part of the device;

FIG. 5 a block diagram of a complete system with four devices or sensorsconnected to a bus; and

FIG. 6 a block diagram of the power modem.

PATHS TO THE EXECUTION OF THE INVENTION

FIGS, 1a, 1b, 1c show a device according to DAB 10, Nov. 3, 1994. Thedevice comprises a frame 1 with a center column 7 as well as a circularcover plate 2 and a base plate 3. The cover plate 2 and the base plate 3exhibit a plurality of holes 5, 5' and, as a rule, six holes. Test tubes6, 6' made of glass are disposed in the holes 5, 5'. The base plate 3 iscovered at its underside with a mesh 4 made of stainless steel wire. Theplates 2, 3 are rigidly separated from one another by vertical metalrods, not shown, at the outer side of the frame 1. For the dissolutiontesting, in each case one tablet or capsule are placed into each testtube 6, 6', and a disk 8, having precisely defined recesses 9, is placedonto the tablet or capsule to weight the tablet or capsule, and thedissolution time is measured.

The mechanical modification of the parts which are changed relative tothe apparatus according to DAB 10 is shown in FIGS. 2 and 3.

Holes 11 are disposed on a base plate 10, corresponding to the baseplate 3 of FIG. 1, wherein the holes 11 have the same distance from thecenter point of the base plate 10 as well as the same distance from eachother. A coil 12 is disposed around each hole 11, wherein the windingends lead to contacts 13, 14. Thus, the base plate forms the coilsupport 10. The coils 12 are integrated into the base plate. The coilsupport 10 can however also be formed as an intermediate base plate.

Each one of the coils is formed as a flat coil 12, wherein one half ofthe windings of the flat coil are integrated into the upper side and theother half into the underside or bottom of the base plate 10. The lines13, 14 to the coils are formed congruent relative to the upper side andthe underside of the base plate 10. The winding ends 13, 14 lead aboveand below the base plate to contact pins of a plug according to FIG. 2.The lines are guided upwardly in the center column 7.

A conductor loop 16 is disposed on a surface of a disk 15 or isintegrated into the disk 15, wherein the disk corresponds in itsdimensions and its density to the disk 8 according to DAB 10.

According to FIG. 4, the coils 12 are in each case part of LCoscillation circuits 17, wherein the coils 12 are excited and energizedwith a square-wave generator 24 via an analog multiplexer 18. Theindividual oscillation circuit is path-dependently dampened with theconductor loop 16, disposed in the disk 15. Since the resonancefrequency of the oscillation circuit 17 is selected much higher than theexciter frequency of the square-wave generator 24, a decayingoscillation of the oscillation circuit 17 occurs after each slope of theexciter signal. The stronger the damping of the oscillation circuit 17,the faster the oscillations decay. Thereby, the area of the enveloperepresents a measure for the damping of the oscillation circuit 17. Therealization of the capturing of the values to be measured is performedby feeding the square-wave voltage of the square-wave generator 24 withthe analog multiplexer 18 to the LC oscillation circuit 17 of thedevice. The voltage, resulting within the oscillation circuit 17, isagain fed with the multiplexer 18 to an amplifier 25. The inherentlosses of the oscillation circuit 17 can in part be compensated for witha positive feedback of the amplifier output to the input.

The determination of the envelope area of the oscillation circuitvoltage occurs by rectification and subsequent low-pass filtering 26 ofthe amplified oscillation circuit voltage. The output voltage of thelow-pass filter 26 is fed to a analog/digital A/D transformer 27,wherein the output signal of the transformer 27 is sent to amicrocontroller 19. The microcontroller calculates the distance of thecorresponding disk 15 to the base of the frame 1 from the voltage valuesreceived. Correction factors can be automatically determined by thesoftware of the microcontroller 19 in a calibration process and storedin a non-volatile memory storage 28, wherein the non-volatile memorystorage 28 is preferably an EEprom.

The distance values are continuously recorded during thedissolution-time determination of the tablets or capsules and aretransmitted based on an inductive coupling path to an evaluationcomputer 23, FIG. 5.

According to FIG. 5, the energy supply and data transfer between theframe 1 and the evaluation device 23 is preferably performed contactlessby a magnetic field. For this purpose, the electric coupling path iscomprised in each case of one half of a pot core with an inserted coil35 on the side of the sensor support 34, i.e. the driving side for theframe, as well as of a pot core half with the coil 36 on the sensorside. The pot core and the coil 35 are integrated into the sensorsupport 34 in the support for the frame. The shell-type-core half andthe coil 36 are integrated into the center column of the respectiveframe on the side of the frame 1 or, respectively, of the sensor.

The energy transfer and the data transfer to the coils 12 can occursimultaneously through the coupling-coil path 35-36 at differentfrequencies, whereby a separation of the energy transfer and datatransfer is possible with a filter. The energy transfer is performed byapplying a 20-kHz alternating voltage of a sine generator 31 to theprimary side of a transmitter-receiver coil 29 of the coupling path or,respectively, of the transmitter. The secondary-induced voltage isrectified and stabilized behind a low-pass filter 30 for the separationof the data signal.

In addition, the connection of the sensor supports 34 to the energy anddata bus 21 can be seen on FIG. 5. The sensors comprise in each case anoscillation circuit 17, an evaluation device 20, 23, as well as aninductive energy and data coupling by means of the coupling-coil path35-36 and the sensors are switched to a common bus 21 and can receive abus address. For this purpose, a transport address is inserted into themessage to be delivered.

The data transfer can be performed according to FIGS. 5 and 6 by way ofa half-duplex operation with a modem 20 on each side of the couplingpath. The respective data transmitter modulates a carrier frequency,preferably in AM or in FSK, of 130 kHz and switches the signal with apower amplifier 32 to the winding of the transmitter. The receiver sidefeeds the output voltage of the transmitter through a high-pass filter33 to the input of the modem 20. The modem demodulates the signal andwins back the bit current of the transmitter.

The parallel operation of several devices or, respectively, frames ispossible with one power modem 20 based on the insertion of the transportaddress into the messages. The devices are initially individuallyconnected to the bus 21 and receive a bus address. The paralleloperation at the bus occurs once all devices have received an address.

Industrial Applicability

The device is employed in particular for determining the dissolutiontime of medication in pressed form according to "Deutsches Arzneibuch"DAB, European Pharmacopoeia or United States Pharmacopoeia USP. Theusefulness and the advantages of the invention reside in particular inthat a contactless and continuous recording of the motion of the disksand thus the dissolution of the medication in pressed form, such astablets, pills, or capsules, within the test tubes is possible accordingto the invention, in order to determine electrically the currentthickness of the medication from these recordings during the dissolutionprocess and the dissolution time.

    ______________________________________                                        List of Reference Numerals:                                                   ______________________________________                                        1            Frame                                                            2            Cover plate                                                      3            Base plate                                                       4            Mesh                                                             5, 5'        Holes                                                            6, 6'        Test tubes                                                       7            Center axle or column                                            8            Disk                                                             9            Recesses                                                         10           Coil support or base plate                                       11           Holes                                                            12           Coils                                                            13, 14       Contacts                                                         15           Disk                                                             16           Conductor loop                                                   17           Oscillation circuits                                             18           Multiplexer                                                      19           Microcontroller                                                  20           Modem or, respectively, power modem                              21           Bus                                                              22           Machine control                                                  23           Evaluation computer                                              24           Square-wave generator                                            25, 32       Amplifier                                                        26           Low-pass filter                                                  27           A/D transformer                                                  28           Non-volatile memory storage                                      29           Transmitter-receiver coil                                        30           Low-pass filter                                                  31           Sine generator                                                   33           High-pass filter                                                 34           Sensor supports                                                  35, 36       coupling coils or coupling-coil path                             ______________________________________                                    

What is claimed is:
 1. A device for determining the dissolution time ofmedications in pressed form comprisinga frame; a center column furnishedat the frame; a base plate furnished at the frame, wherein the baseplate is furnished with a plurality of holes; a mesh covering the holesfrom below, test tubes placed upright in the holes and located withinthe frame, a plurality of disks, with each of the disks insertable intoeach one of the test tubes for loading and weighting the individualmedications, a plurality of electric coils, with each one of theelectric coils disposed around a corresponding one of the holes,whereineach electric coil forms part of one of a plurality of electricaloscillation circuits, a plurality of conductor loops, with eachconductor loop disposed near a corresponding one of the plurality ofdisks for path-dependently damping the electrical oscillation circuits,wherein each electric coil and each conductor loop are connected to anelectric power supply to generate oscillations and to an evaluationdevice for evaluating measurement results.
 2. The device according toclaim 1, wherein each one of the plurality of electric coils is formedas a single-layer coil.
 3. The device according to claim 1, wherein eachone of the plurality of electric coils is formed as a multi-layer coil.4. The device according to claim 1, further comprisinga coil support,wherein each electric coil is a flat coil having windings, wherein afirst half of the windings of the flat coil are integrated into an upperside and a second half into a bottom side of the coil support, andwherein feed lines to the electric coils are formed congruent relativeto the upper side and the bottom side of the coil support.
 5. The deviceaccording to claim 1, further comprisinga coil support, wherein eachelectric coil is a flat coil having windings, wherein a first half ofthe windings of the flat coil are integrated into an upper side and asecond half into a bottom side of the base plate of the frame, andwherein feed lines to the electric coils are formed congruent relativeto the upper side and the bottom side of the base plate.
 6. The deviceaccording to claim 1, further comprisinga multi-layer plate, wherein theelectric coils are disposed in multi-layer technique on the multi-layerplate.
 7. The device according to claim 1, wherein the electric coilsare disposed separated from the base plate of the frame.
 8. The deviceaccording to claim 1, further comprisinga multiplexer connected to theelectrical oscillation circuits, wherein the electrical oscillationcircuits are controllable with the multiplexer.
 9. The device accordingto claim 1, further comprisinga drive unit; a source of a magnetic fielddisposed between the frame and the drive unit, wherein an energy supplyand a data transfer is performed contactless by means of a magneticfield between the frame and a drive unit, wherein the frame is supportedwith the center column disposed within the drive unit.
 10. The deviceaccording to claim 9, further comprisinga plurality of pot cores,wherein an electric coupling path is in each case comprised of one halfof a corresponding one of the plurality of pot cores having a respectiveelectric coil inserted on each side, wherein a first pot-core half withelectric coil disposed on a driving side is integrated into a supportfor the center column, and on a side of the frame a second pot-core halfwith electric coil is integrated into the center column.
 11. The deviceaccording to claim 9, further comprisinga plurality of pot cores,wherein an electric coupling path is in each case comprised of one halfof a corresponding one of the plurality of pot cores; having arespective electric coil inserted on each side, wherein a first pot-corehalf with electric coil disposed on a driving side is integrated into asupport for the frame, and on a side of the frame a second pot-core halfwith electric coil is integrated into the center column.
 12. The deviceaccording to claim 1, further comprisinga common bus; a plurality offrames each comprised of an oscillation circuit, an evaluation device,and an inductive energy coupling and a data coupling, are switched tothe common bus and receive a bus address, and wherein a transportaddress is inserted into a message to be delivered for a paralleloperation of the frames at the common bus.
 13. The device according toclaim 1, further comprisinga common bus; a plurality of sensors eachcomprised of an oscillation circuit, an evaluation device, and aninductive energy coupling and a data coupling, are switched to thecommon bus and receive a bus address, and wherein a transport address isinserted into a message to be delivered for a parallel operation of thesensors at the common bus.
 14. The device according to claim 13, whereineach oscillation circuit includes a transmitter coil and a receivercoil, wherein the transmitter coils and the receiver coils of thesensors for coupling to a driving side of the frames are operated withdiffering frequencies for a separation of an energy flow and a dataflow.
 15. A method for determining the dissolution time of medication inpressed form comprisingconnecting a plurality of electric coils and aplurality of conductor loops to an electric power supply; placing amedication in pressed form into each one of a plurality of test tubes,wherein the test tubes are located in a frame, wherein a center columnis furnished at the frame, and wherein a base plate is furnished at theframe, wherein the base plate is furnished with a plurality of holes,wherein a mesh is covering the holes from below, and wherein the testtubes are placed upright in the holes and located within the frame;inserting each one of a plurality of disks into each one of the testtubes for loading and weighting the individual medications; energizingthe plurality of electric coils, wherein each one of the electric coilsis disposed around a corresponding one of the holes, and wherein eachelectric coil forms part of an electrical oscillation circuit; dampingthe electrical oscillation circuit with a plurality of conductor loops,wherein each conductor loop is disposed on a corresponding one of theplurality of disks for path-dependently damping the electricaloscillation circuit; generating oscillations in each electric coil andin each conductor loop with power furnished by the electric powersupply; feeding the oscillations to an evaluation device for evaluatingthe measurement of the dissolution time of the medication.
 16. A methodfor determining the dissolution time of medication in pressed formcomprisingconnecting a plurality of electric coils and a plurality ofconductor loops to an electric power supply; placing a medication inpressed form into each one of a plurality of test tubes, wherein thetest tubes are located in a frame, wherein a center column is furnishedat the frame, and wherein a base plate is furnished at the frame,wherein the base plate is furnished with a plurality of holes, wherein amesh is covering the holes from below, and wherein the test tubes areplaced upright in the holes and located within the frame; inserting eachone of a plurality of disks into each one of the test tubes for loadingand weighting the individual medications; energizing the plurality ofelectric coils, wherein each one of the electric coils is disposedaround a corresponding one in the base plate, and wherein each electriccoil forms part of an electrical oscillation circuit; damping theelectrical oscillation circuit with a plurality of conductor loops,wherein each conductor loop is disposed on a corresponding one of theplurality of disks for path-dependently damping the electricaloscillation circuit; generating oscillations in each electric coil andin each conductor loop with power furnished by the electric powersupply; feeding the oscillations to an evaluation device for evaluatingthe measurement of the dissolution time of the medication.
 17. A methodfor determining the dissolution time of medication in pressed formcomprisingconnecting a plurality of electric coils and a plurality ofconductor loops to an electric power supply; placing a medication inpressed form into each one of a plurality of test tubes, wherein thetest tubes are located in a frame, wherein a center column is furnishedat the frame, and wherein a base plate is furnished at the frame,wherein the base plate is furnished with a plurality of holes, wherein amesh is covering the holes from below, and wherein the test tubes areplaced upright in the holes and located within the frame; inserting eachone of a plurality of disks into each one of the test tubes for loadingand weighting the individual medications; energizing the plurality ofelectric coils, wherein each one of the electric coils is disposedaround a corresponding in the base plate, and wherein each electric coilforms part of an electrical oscillation circuit; damping the electricaloscillation circuit with a plurality of conductor loops, wherein eachconductor loop is disposed in a corresponding one of the plurality ofdisks for path-dependently damping the electrical oscillation circuit;generating oscillations in each electric coil and in each conductor loopwith power furnished by the electric power supply; feeding theoscillations to an evaluation device for evaluating the measurement ofthe dissolution time of the medication.
 18. A method for determining thedissolution time of medication in pressed form comprisingconnecting aplurality of electric coils and a plurality of conductor loops to anelectric power supply; placing a medication in pressed form into eachone of a plurality of test tubes, wherein the test tubes are located ina frame, wherein a center column is furnished at the frame, and whereina base plate is furnished at the frame, wherein the base plate isfurnished with a plurality of holes, wherein a mesh is covering theholes from below, and wherein the test tubes are placed upright in theholes and located within the frame; inserting each one of a plurality ofdisks into each one of the test tubes for loading and weighting theindividual medications; energizing the plurality of electric coils,wherein each one of the electric coils is disposed around acorresponding one of the holes, and wherein each electric coil formspart of an electrical oscillation circuit; damping the electricaloscillation circuit with a plurality of conductor loops, wherein eachconductor loop is disposed in a corresponding one of the plurality ofdisks for path-dependently damping the electrical oscillation circuit;generating oscillations in each electric coil and in each conductor loopwith power furnished by the electric power supply; feeding theoscillations to an evaluation device for evaluating the measurement ofthe dissolution time of the medication.